Aetiology of TemporaL Arteritis Study (ATLAS)
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|ClinicalTrials.gov Identifier: NCT02584517|
Recruitment Status : Not yet recruiting
First Posted : October 22, 2015
Last Update Posted : October 22, 2015
|Condition or disease|
Objectives and Study Plan:
The purpose of the study is to investigate the underlying immunological processes in GCA and to study the pattern of expression of immune response over time to give us information about how best to monitor GCA.
The end point will be the final visit of the final patient.
The project is in 3 phases. In phase 1 (0-2 years) patients will be recruited to fulfil the specified primary and secondary objectives. In phase 2 (0-4 years), these patients will be followed up for a total of 2 years each, or until they are discharged from clinic. In phase 3 (1-5 years), further studies will be defined and tissue and data collected under amended ethics.
|Study Type :||Observational|
|Estimated Enrollment :||200 participants|
|Official Title:||Understanding the Aetiology and Pathogenesis of Giant Cell Arteritis|
|Study Start Date :||January 2016|
|Estimated Primary Completion Date :||January 2018|
|Estimated Study Completion Date :||January 2021|
Patients referred with suspected GCA, whose final diagnosis is GCA
Patients referred with suspected GCA, whose final diagnosis is another disorder
- Phenotyping of innate lymphoid cells (ILC) in the arterial wall and blood of patients with GCA [ Time Frame: 24 months ]Arterial biopsy tissue and peripheral blood will be collected from patients with suspected GCA. A proportion of these will be diagnosed with GCA and will be the "test" subjects, and a proportion will be diagnosed with other conditions that are not GCA and will be the "controls". We will use immunohistochemistry and immunofluorescence microscopy to locate and phenotype ILC in arterial biopsies. We will use semi-quantitative methods (ie cells per random high powered field) to compare prevalence of ILC in tests and controls. We will also isolate peripheral blood mononuclear cells (PBMCs) from fresh whole blood, and stain the cells to use flow cytometry to quantify and phenotype the ILC. Tests and Controls will be compared using Mann-Whitney statistical testing.
- CD70 in GCA [ Time Frame: 12 months ]CD70 is a costimulatory molecule which is present for a short time on the surface of activated T cells. CD70 has been studied in other autoimmune conditions such as systemic lupus, where it is involved in generating the self-reactive factors responsible for the disease. It is therefore suggested that it might be involved in the development of another autoimmune vasculitis, GCA. We will quantify and phenotype CD70+ve cells in peripheral blood and biopsies of patients with GCA and in controls. We will also measure the levels of the soluble form of its receptor, CD27, in patients and controls.
- IL-7 and sIL-7R in GCA [ Time Frame: 36 months ]IL-7 is a key cytokine for development of all lymphoid cells, including ILC. Levels of sIL-7R have been linked to active renal disease in systemic lupus, and sIL-7R is suggested as a biomarker of lupus. We will collect serum at several time points from patients with GCA and controls (see primary outcome measures). The level of IL-7 and sIL-7R will be quanitified by Enzyme-linked Immunosorbent Assay (ELISA) and the results plotted as time series. We will analyse the trends of these series to see how useful IL-7 and sIL-7R may be in monitoring GCA.
- Vascular Endothelial Growth Factor (VEGF) levels over time [ Time Frame: 36 months ]VEGF is a putative biomarker of GCA. We will collect serum at several time points from patients with GCA and controls (see primary outcome measures). The level of VEGF will be quanitified by Enzyme-linked Immunosorbent Assay (ELISA) and the results plotted as time series. We will analyse the trends of these series to see how useful VEGF may be in monitoring GCA.
- Pentraxin 3 levels over time [ Time Frame: 36 months ]Pentraxin 3 is a second biomarker of interest in GCA, and we plan to analyse its expression in peripheral blood as for VEGF.
- Archiving of tissue for future studies [ Time Frame: 60 months+ ]The cohort of patients recruited to this study represents a valuable resource for future ethically-approved studies of the aetiology of GCA. We believe that the majority of patients would like their donations to contribute to as much research as possible. Therefore we will archive tissue in the form of blood fractions and temporal artery biopsy specimens, as well as linking to anonymized clinical and imaging data. It is planned that the study ethics will be amended with novel substudies as they are designed.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02584517
|Contact: Raashid A Luqmani, DM FRCPemail@example.com|
|Contact: Jana Vaskovafirstname.lastname@example.org|
|Principal Investigator:||Raashid A Luqmani, DM FRCP||University of Oxford|